Surface-enhanced Raman sensors: Early history and the development of sensors for quantitative biowarfare agent and glucose detection

Surface-enhanced Raman spectroscopy (SERS) is a powerful technique for the sensitive and selective detection of low-concentration analytes. This paper includes a discussion of the early history of SERS, the concepts that must be appreciated to optimize the intensity of SERS and the development of SERS-based sensors. In order to achieve the lowest limits of detection, both the relationship between surface nanostructure and laser excitation wavelength, as well as the analyte/surface binding chemistry, must be carefully optimized. This work exploits the highly tunable nature of nanoparticle optical properties to establish the first set of optimization conditions. The SERS enhancement factor, EF_SERS, is optimized when the energy of the localized surface plasmon resonance (LSPR) lies between the energy of the excitation wavelength and the energy of the vibrational band of interest. With the narrow LSPRs used in this work, it is straightforward to achieve EF_SERS ∼ 10 ⁸. These optimization conditions were exploited to develop SERS-based sensors for two important target molecules: a Bacillus anthracis biomarker and glucose in a serum protein mixture. Using these optimized film-over-nanosphere surfaces, an inexpensive, portable Raman spectrometer was used successfully to detect the infectious dose of Bacillus subtilis spores with only a 5-s data collection. The biomarker used to detect the Bacillus subtilis spores binds irreversibly to SERS substrates, whereas other important biomolecules, such as glucose, do not have any measurable binding affinity to a bare silver surface. To overcome this difficulty, a biocompatible partition layer was self-assembled on the SERS substrate before exposure to the analyte solution. Using the partition layer approach to concentrate glucose near the SERS-active substrate, physiological glucose concentrations can be detected even in the presence of interfering serum proteins.